Decreases in TGF-β1 and PDGF levels are associated with echocardiographic changes during adjuvant radiotherapy for breast cancer.

Background: Radiation-induced heart disease is mainly caused by activation of the fibrotic process. Transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are pro-fibrotic mediators. The aim of our study was to evaluate the behavior of TGF-β1 and PDGF during adjuvant radiotherapy (RT) for breast cancer and the association of these cytokines with echocardiographic changes.

Methods: Our study included 73 women with early-stage breast cancer or ductal carcinoma in situ (DCIS) receiving post-operative RT but not chemotherapy. TGF-β1 and PDGF levels in serum samples taken before and on the last day of RT were measured by an enzyme-linked immunosorbent assay. Echocardiography was also performed at same time points. Patients were grouped according to a ≥ 15% worsening in tricuspid annular plane systolic excursion (TAPSE) and pericardium calibrated integrated backscatter (cIBS).

Results: In all patients, the median TGF-β1 decreased from 25.0 (IQR 21.1-30.3) ng/ml to 23.6 (IQR 19.6-26.8) ng/ml (p = 0.003), and the median PDGF decreased from 18.0 (IQR 13.7-22.7) ng/ml to 15.6 (IQR 12.7-19.5) ng/ml (p < 0.001). The baseline TGF-β1, 30.7 (IQR 26.0-35.9) ng/l vs. 23.4 (IQR 20.1-27.3) ng/l (p < 0.001), and PDGF, 21.5. (IQR 15.7-31.2) ng/l vs. 16.9. (IQR 13.0-21.2) ng/ml, were higher in patients with a ≥ 15% decrease in TAPSE than in patients with a < 15% decrease. In patients with a ≥ 15% decrease in TAPSE, the median TGF-β1 decreased to 24.7 (IQR 20.0-29.8) ng/ml (p < 0.001), and the median PDGF decreased to 16.7 (IQR 12.9-20.9) ng/ml (p < 0.001). The patients with a < 15% decrease had stable TGF-β1 (p = 0.104), but PDGF decreased to 15.1 (IQR 12.5-18.6), p = 0.005. The patients with a ≥ 15% increase in cIBS exhibited a decrease in TGF-β1 from 26.0 (IQR 21.7-29.7) to 22.5 (IQR 16.6.-26.7) ng/ml, p < 0.001, and a decrease in PDGF from 19.8 (IQR 14.6-25.9) to 15.7 (IQR 12.8-20.2) ng/ml, p < 0.001. In patients with a < 15% increase, TGF-β1 and PDGF did not change significantly, p = 0.149 and p = 0.053, respectively.

Conclusion: We observed a decrease in TGF-β1 and PDGF levels during adjuvant RT for breast cancer. Echocardiographic changes, namely, in TAPSE and cIBS, were associated with a greater decrease in TGF-β1 and PDGF levels. Longer follow-up times will show whether these changes observed during RT translate into increased cardiovascular morbidity.